Richard Spritz, M.D. Program Director

Mapping, discovery, and function of disease genes affecting skin and craniofacial development and autoimmunity

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My laboratory studies the molecular basis of human genetic diseases, including mapping, discovery, and mutational and functional analysis of human disease genes. Over the past 20 years we have characterized a number of single-gene genetic disorders of pigmentation such as albinism (OCA), in which little or no melanin pigment is made due to functional defects of melanocytes, piebaldism, a defect of development in which neural crest-derived melanocytes, and a series of disorders of organelle biogenesis in which pigment-forming melanosomes ore incorrectly assembled.

For the past decade, my lab has focused on the most common pigmentation disorder, vitiligo, a polygenic autoimmune disease in which melanocytes are destroyed by the immune system, giving rise to patches of white skin and hair. Vitiligo is epidemiologically associated with several other autoimmune diseases, autoimmune throid disease, type 1 diabetes, rheumatoid arthritis, and others, suggesting that these different autoimmune diseases share common underlying susceptibility genes. We have carried out a number of types of studies to identify these genes. Most recently, we carried out a genomewide association study of thousands of vitiligo patients, identifying at least 17 different genes that are involved with susceptibility to vitiligo, and some of these have also been implicated in causing other autoimmune diseases. We are currently trying to identify causal mutations in these genes by "NextGen" DNA sequencing and genetic studies involving a large number of vitiligo patients from various different ethnic groups.

We are also studying one of the most common of all major birth defects, cleft lip and palate. We previously chaarcterized patterns of gene expression in the developing mouse face, and are currently using the mouse "Collaborative Cross" to map and identify genes responsible for major components of normal facial shape. In parallel, we are carrying out fine scale morphometric measurments of large numbers of normal children from different populations (European white, Hispanic-Latino, east Asian, African), in which we will carry out a parallel genetic analysis to identify major genes that determine facial shape. We anticipate that this parallel study of facial shape determinants in mouse and human will identify key genes, some of which may also be of importance in the pathogenesis of cleft lip and palate.